Curcuminoids in Combination Docetaxel for the Treatment of Cancer and Tumour Metastasis

a technology of curcuminoids and docetaxel, which is applied in the direction of biocide, plant/algae/fungi/lichens, plant compositions, etc., can solve the problems of limited entry and effectiveness of chemotherapeutics, significant morbidity and mortality, and poor prognosis of glioblastoma patients, so as to enhance the clinical efficacy of docetaxel

Inactive Publication Date: 2014-05-08
INST NAT DE LA SANTE & DE LA RECHERCHE MEDICALE (INSERM)
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Cancer is a deadly disease causing significant morbidity and mortality.
However, glioblastoma patients still have very poor prognosis due to incomplete resection and resistance to radio- and chemotherapy largely due to endothelial cells of the >(BBB) that limits entry and effectiveness of chemotherapeutics through expression of P-glycoprotein (see Barthomeuf et al.
However up to now, DTX and curcuminoids have never been associated clinically for treatment of cancers.

Method used

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  • Curcuminoids in Combination Docetaxel for the Treatment of Cancer and Tumour Metastasis

Examples

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example 1

Preclinical Studies

[0024]Materials & methods:

[0025]Materials: Cell culture media were obtained from Gaithersburg, Md. or Life Technologies (Burlington, Ontario, Canada). Fetal bovine calf serum was purchased from Hyclone Laboratories (Logan, Utah). Curcumin and DTX were from Sigma (St-Louis, Miss.). Goat anti-human survivin was from Santa Cruz Biotechnology Inc. (Santa Cruz, Calif.) and mouse monoclonal antisera directed against HIF-1α from BD Transduction Laboratories (Alphen and Rijn, The Netherlands). Horseradish peroxidase-coupled antimouse secondary antibodies were purchased from Jackson Immuno-Research Laboratories (West Grove, Pa.) or Dako (Dako, Glostrup, Denmark). Mouse monoclonal anti-β-Actin and cyclosporin A was from Sigma-Aldrich Chimie and enhanced chemoluminescence (ECL) reagents were from Perkin Elmer Life Sciences (Boston, Mass.). 3[H]-VBL (11.3 Ci / mmol) was from Amersham Pharmacia Biotech (Oakville, Ontario). The intra- and extra-cellular platelet activating factor...

example 2

Clinical Study

[0056]Protocol:

[0057]14 patients (age 53-82, median 71) with metastatic breast adenocarcinoma (WHO performance status ≦2 prior therapy regimen, adequate organ function) were enrolled between January 2007 and April 2008. All have signed informed consent. They were treated in first line chemotherapy by docetaxel (Taxotere®, DTX) accordingly to the schedule of administration accepted by EMEA: IV perfusion 100 mg / m2 every 21 days for 6 cycles.

[0058]Curcuminoids were administered orally at 500 mg and escalated until Maximum Tolerated Dose (MTD) was reached. The administered dose varied from 500 mg to 8 g / day. Each dose was given to 1 patient per level until a DLT occurred. In this case, the level was documented on at least 3 patients. In practice, curcuminoids were given as follows: 500 mg, 1 g, 2 g, 4 g, 6 g or 8 g during 7 days, then stopped for 14 days. Ingestion started 4 days before DTX administration, was maintained the day of administration and, finished two days lat...

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Abstract

The present invention relates to a curcuminoid for enhancing the clinical efficacy of Docetaxel for the treatment of cancers and metastases.

Description

FIELD OF THE INVENTION[0001]The present invention relates to the field of cancer and tumour metastasis treatment.BACKGROUND OF THE INVENTION[0002]Cancer is a deadly disease causing significant morbidity and mortality. In 2007, breast cancer has been estimated as the first (worldwide, developed countries) or second (developing countries) cause of cancer-related death in female (Garcia M et al. Global cancer Facts and FIGS. 2007, Edited by AACR.) It affects approximately one out of thirty-nine to one out of three women who reach age ninety in the Western world. Prostate cancer has been estimated to be the first cause of new cancer cases and the fifth cause of cancer-related death in males from developed countries (Garcia M et al. 2007). Finally, the most malignant tumour of the human nervous system: glioblastoma [World Health Organization (WHO) Grade IV] is one of the most lethal tumours. It is the most common cause of cancer-related death in childwood and the first cause of primary b...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): A61K31/12A61K31/704
CPCA61K31/704A61K31/12A61K31/337A61K36/9066A61P35/00A61P35/04
Inventor BARTHOMEUF, CHANTALCHOLLET, PHILIPPEBAYET-ROBERT, MATHILDE
Owner INST NAT DE LA SANTE & DE LA RECHERCHE MEDICALE (INSERM)
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